The present invention relates to dextran whose boron content is reduced, a process for producing the same, and dextran with which a container is filled in a solution state.
Dextrans are polysaccharides produced by fermentation of sucrose using bacteria capable of producing dextran (e.g. Leuconostoc mesenteroides, Leuconostoc dextranicum, etc.). Those having a proper molecular weight among produced dextrans have hitherto been used as substitute plasma in a treatment on acute bleeding, preventive and remedy for surgical shock due to injury or bleeding, or external perfusate in an operation, after being dissolved in an isotonic sodium chloride solution. A complex with iron as a derivative of dextran is used as an injection to iron-deficiency anemia. A sulfate ester of dextran is used as a blood coagulant in place of heparin. Also, dextrans have been used in various industrial fields such as food industry.
Dextran is generally produced through production processes as shown in FIG. 2. First, sucrose as a raw material and an inorganic salt such as dipotassium phosphate are charged in a raw material dissolution vessel 1, together with vitamins and water, and then dissolved. The raw material solution is supplied to a fermentation vessel 2, where the solution is fermented by adding bacteria capable of producing dextran. After the completion of fermentation, the fermented solution is supplied to a precipitation vessel 3, where dextran is precipitated by adding methanol and then separated.
In a hydrolysis vessel 4, hydrolysis is conducted by adding hydrochloric acid, and then impurities are removed by using a filter 5. A dextran section, which is precipitated at a fixed methanol concentration, is collected in a fractional precipitation vessel 6 and, after dissolving the dextran section in a dissolution vessel 7, salts are removed in an ion exchange column 8. Dextran is dissolved again in a dissolution vessel 9, and then supplied to a spray dryer 13 via a filter 10, an evaporator 11 and a control tank 12, followed by spray drying to obtain a dextran powder.
The dextran powder thus obtained is used as an injection in the medical field, after it was dissolved in an isotonic sodium chloride solution and a container is filled with it and then sealed, as described above. However, when dextrin obtained by a conventional process is dissolved and a container is filled with the resulting solution, there arises a problem that a crystal of dextran is liable to be deposited as a result of a change in temperature during the storage or transportation.
When using a dextran solution as substitute plasma or external perfusate, it is necessary that a crystal of dextran is not deposited in the dextran solution.
However, since it is difficult to dissolve once deposited crytal of dextran again even when using means such as heating or shaking, an injection container filled with a dextran solution containing a deposited crystal must be discarded.
It is, therefore, an object of the present invention to provide dextran which hardly causes deposition of a crystal even when using in the form of a solution, a process for producing the same, and dextran with which a container is filled in a solution state.
The present inventors have studied intensively to solve the above problems and studied furthermore on the assumption that impurities contained in dextran produced by a conventional process exert an influence on deposition of a crystal of dextran. As a result, they have obtained such a novel finding that boron contained in dextran has a function of accelerating deposition of dextarn, surprisingly.
On the basis of such a finding, the present inventors have studied furthermore and found a fact that deposition of a crystal from a dextran solution is inhibited or drastically reduced by controlling the content of boron in dextran to a value less than 0.30 xcexcg/g (dry basis) calculated on the basis of boron atom. Thus, the present invention has been completed.
That is, the present invention includes the following inventions:
(1) Dextran whose boron content is reduced, said boron content being less than 0.30 xcexcg/g (dry basis) calculated on the basis of boron atom;
(2) Dextran according to the term (1), wherein said boron content is not more than 0.20 xcexcg/g (dry basis) calculated on the basis of boron atom;
(3) Dextran according to the term (1) or (2), with which a container is filled in a solution state;
(4) Process for producing dextran whose boron content is reduced, which comprises treating a boron-containing dextran with a lower alcohol, thereby to reduce the boron content to a value less than 0.30 xcexcg/g (dry basis) calculated on the basis of boron atom; and
(5) The process according to the term (4), wherein said boron-containing dextran as a starting material is in the form of a powder or an aqueous solution and is treated with a lower alcohol.
The term xe2x80x9cboron contentxe2x80x9d used in the present invention refers to a value (xcexcg) wherein an amount of boron based on a dry weight (g) of dextran contained in a powder or solution of dextran of the present invention is represented by calculation on the basis of boron atom.